Quantitative Profiling of Nanoscale Liposome Deformation by a Localized Surface Plasmon Resonance Sensor

Abstract

Characterizing the shape of sub-100 nm, biological soft-matter particulates (e.g., liposomes and exosomes) adsorbed at a solid-liquid interface remains a challenging task. Here, we introduce a localized surface plasmon resonance (LSPR) sensing approach to quantitatively profile the deformation of nanoscale, fluid-phase 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) liposomes contacting a titanium dioxide substrate. Experimental and theoretical results validate that, due to its high sensitivity to the spatial proximity of phospholipid molecules near the sensor surface, the LSPR sensor can discriminate fine differences in the extent of ionic strength-modulated liposome deformation at both low and high surface coverages. By contrast, quartz crystal microbalance-dissipation (QCM-D) measurements performed with equivalent samples were qualitatively sensitive to liposome deformation only at saturation coverage. Control experiments with stiffer, gel-phase 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) liposomes verified that the LSPR measurement discrimination arises from the extent of liposome deformation, while the QCM-D measurements yield a more complex response that is also sensitive to the motion of adsorbed liposomes and coupled solvent along with lateral interactions between liposomes. Collectively, our findings demonstrate the unique measurement capabilities of LSPR sensors in the area of biological surface science, including competitive advantages for probing the shape properties of adsorbed, nanoscale biological particulates.

A model derived from hydrodynamic simulations for extracting the size of spherical particles from the quartz crystal microbalance

“…Since our focus is on spherical particles, we mix the vesicles in a buffer solution, with a relatively low ionic strength: 75 mM, which reduces the adhesion force, and induces a negative osmotic pressure, that counteracts and minimizes possible shape deformations39 . A previous study, based on QCM-D and localized surface plasmon resonance experiements, showed that under similar ionic strength/osmotic pressure conditions, SUVs adhere firmly to the TiO 2 surface and remain nearly spherical 35.…”

“…23 24 Assuming the height of this layer to be equal to the particle size, the latter is estimated using the Sauerbrey relationship. Despite a few agreements with alternative size measurements, 35,36 there is no rigorous theoretical basis to relate the particle size to -Δf in the ΔΓ = 0 limit, and it remains an open question as to why the extrapolation method works in certain cases, while it is unsuccessful in other cases.…”

Calcium Dependent Reversible Aggregation of Escherichia coli Biomimicking Vesicles Enables Formation of Supported Vesicle Layers on Silicon Dioxide

“…This surface sensitive technique detects the total mass of matter adsorbed on the sensor surface (Konradi et al, 2012) while NPS is able to detect adsorbed matter with a different RI than the background solution. Therefore, vesicles including the mass of the entrapped solution are detected with QCM, which is often used for evaluation of the type of formed lipid layer, i.e., SLB or SVL (Jackman et al, 2017b). Additionally, QCM has roughly one order of magnitude higher sensing depth compared to NPS, which extends a few hundred nanometers above the sensor surface.…”

Nanoarchitectonic‐Based Material Platforms for Environmental and Bioprocessing Applications

“…However, one general challenge of the QCM−D technique is that the measurement signals are not proportional to the surface coverage of adsorbed vesicles . The nonlinear responses occur due to the motion of adsorbed vesicles and hydrodynamically‐coupled solvent along with lateral interactions between adsorbed vesicles . As such, conventional QCM−D models are generally limited to saturation coverage and treat the adsorbed vesicle layer as a homogenous film .…”